Dental students to research drugs role in cleft lip and palate

Dental students to research drugs role in cleft lip and palate

The University of Dundee's international reputation for work into cleft lip and palate has brought with it a major research opportunity for two final year dental students. Andrew Neison (22) from Largs and Andrew Rennie (22) from Peterborough in East Anglia have been awarded $5,000 by an American charity known as The Smile Train, which is dedicated to eradicating the problem of clefts.

The two will be looking for any evidence that smoking, alcohol, anti-depressants and corticosteroids taken during the first months of pregnancy might be associated with the birth of children with cleft lip or palate. Questionnaires have been issued to nearly 500 subjects in an ongoing multi-centred study and the Smiletrain initiative allows the students to carry out analysis of the information which has been collected. Meanwhile a parallel project will be pursued in Australia and data from the two will ultimately be pooled and compared.

The project is one of a cluster of global research initiatives to be developed by Dr Peter Mossey and his team at the University of Dundee centre over the next five years. These will also probe the genetic basis of cleft problems, their treatment and their prevention.

Peter Mossey: "Cleft lip or palate occurs in around one per 500 births worldwide though the ratio varies widely between regions and nations. The emotional upset to individuals and families can be immense, to say nothing of the health implications and the financial costs in terms of extra care. But a great deal of work has been done across the world on the causes of these defects, how they can be treated and how they can be prevented. The interplay of genetic and environmental factors is complex and difficult to tease out but there is an increasing awareness that by collaborating at an international level we can accelerate progress in combating clefting problems."

Maternal smoking has already been extensively studied in relation to clefting problems but with mixed results. Several studies have associated smoking with a much higher risk (two to six fold) but this has failed to show in other investigations. Alcohol is already known to produce a characteristic craniofacial abnormality known as the "foetal alcohol syndrome" leading to suspicions that it could be implicated in clefting malformations but in spite of much study, details remain unclear. Certain drugs including corticosteroids, aspirin, diazepam and retinoids have been implicated in the cause of cleft palate in man through epidemiological studies and are also found to induce cleft palate in laboratory animals making them prime candidates for further investigation.

The Dundee Smiletrain project aims to test if exposure to corticosteroid anti-depressant or anti-anxiolytic drugs in the first three months of pregnancy is associated with a higher incidence of clefting.

This investigation is the latest in a series of intitiatives which have put Dundee University at the forefront in this field. Three years ago Dr Mossey led a collaboration with Aberdeen epidemiologist Professor Julian Little and Edinburgh clinical geneticist Dr David Fitzpatrick to examine the interaction between genes and environment in this disturbing condition. They went on to win funding to establish a European Science Foundation Network to aid collaboration in a multi-disciplinary forum at a European level. A member of the International Task Force for Craniofacial Anomalies Research, Dr Mossey is now one of four individuals who are co-ordinating global research into the problem funded by the World Health Organisation who are putting $2.8 million into "pump priming" initiatives over the next five years.

He is optimistic about what can be achieved: "Understanding the genetic basis of craniofacial anomalies has benefited dramatically over the last decade from the development of recombinant DNA technology. In over 50 such syndromes a gene has either been mapped to a chromosomal location or actively isolated and its structure identified. The recent announcement that mapping of the human genome has been completed means that this is a particularly exciting time for scientists involved in genetic research for multi-factorial disorders.

"Much research so far has involved isolated and independent studies in Europe, USA, Asia and Latin America which make comparisons and evaluations across populations very difficult. As a result there is considerable confusion surrounding the optimal management for even the most common conditions. Multi-centred international collaboration has got to be the way ahead."/